Is BMPER p.Gly136= (c.408C>T) pathogenic?

BMPER p.Gly136= (c.408C>T) is classified Benign/Likely benign in BMPER (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 51.9%, sas) — too common for a highly-penetrant pathogenic allele; Associated with diaphanospondylodysostosis.

What condition is associated with BMPER p.Gly136= (c.408C>T)?

BMPER p.Gly136= (c.408C>T) is associated with diaphanospondylodysostosis (ClinVar).

BMPER p.Gly136=

Q: How common is BMPER p.Gly136= (c.408C>T) in the general population?

BMPER p.Gly136= (c.408C>T) is common (popmax 51.9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.408C>T · rs10265207 · VCV360101

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 51.9%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

diaphanospondylodysostosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.049	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.1	GERP -4.2
Overall
CADD	1.832	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 51.9% South Asian · 47,263/91,006 alleles

Filtering AF 51.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.4%

Overall 46.1% 743,187/1,610,652 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	51.9%	2
Amishnot grpmax-eligible	47.7%	2
European (non-Finnish)	47.2%	2
Remaining individualsnot grpmax-eligible	45.7%	2
East Asian	44.7%	2
Ashkenazi Jewishnot grpmax-eligible	42.9%	2
Middle Eastern	42.9%	2
Admixed American	39%	3
African / African-American	38.6%	3
Finnishnot grpmax-eligible	36.6%	3

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BMPER
Protein: p.Gly136=
Coding: c.408C>T
MANE Select: NM_001365308
dbSNP: rs10265207
Type: single nucleotide variant
Location: chr7:33970334 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 136: the vwfc 2 domain

Full BMPER gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

diaphanospondylodysostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMPER p.Gly136Ser Uncertain significance ★ same residue
BMPER p.Arg241Ter Likely pathogenic ★★ same condition
BMPER p.Gln309Ter Pathogenic ★★ same condition
BMPER p.Ala39Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Ala486Val Uncertain significance ★★ ⚠ same condition
BMPER p.Arg131Cys Uncertain significance ★★ ⚠ same condition
BMPER p.Arg505His Uncertain significance ★★ same condition
BMPER p.Arg582Gln Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bmper-p-gly136 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown